This proposal describes a five year career development plan for an academic career focused on asthma and allergic inflammation. The principal investigator has recently completed residency training in Internal Medicine and fellowship training in Allergy and Immunology and proposes a plan integrating didactic training in signalling and inflammation with mentored supervision of scientific research. The Cleveland Clinic Foundation and Lerner Research Institute provide a unique multidisciplinary environment necessary for the pursuit of this research career development plan. This program will focus on unexplored aspects of inflammation at mucosal surfaces. Dr. Serpil C. Erzurum, Director of the Lung Biology Program, will mentor the principal investigator's scientific development. She is a recognized leader in the field of epithelial cell biology and has trained successful postdoctoral fellows, graduate students, and K award recipients. Dr. S. Jaharul Haque, who has longstanding expertise in intracellular signalling and protein-tyrosine phosphorylation, will serve as co-mentor. The long term goal of this research is to understand the mechanisms by which mast cells contribute to allergic inflammation at mucosal surfaces. Mast cell development is critically dependent upon host cell and T-cell derived factors in end organs, as mast cell functional phenotype is tissue-dependent and varies even within distinct anatomic locations of the same tissue. Experiments in specific aim 1 will investigate the mechanisms by which human airway epithelial cells direct mast cell phenotype by testing the hypothesis that epithelial cells control aspects of mucosal mast cell phenotype independent of T cells. Experiments in specific aim 2 will investigate the activated intracellular signalling components critical for mucosal mast cell development by testing the hypothesis that mucosal mast cell protease phenotype is dependent upon activated STAT3. The Cleveland Clinic Foundation and Lerner Research Institute provide an ideal environment to build a multidisciplinary program studying asthma and allergic inflammation and this integrated program of mentored investigation and didactic training will establish the foundation to build an independent scientific research career.